Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignantly transformed stem cells represent a potential common nidus for the primary cancer and the recurrent cancer that arises after treatment failure. Putative prostate stem cells and prostate tumor stem cells in benign and malignant human prostate tissue, in primary human prostate xenografts, and in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, are defined by expression of breast cancer resistance protein (BCRP), a marker of pluripotent hematopoietic, muscle, and neural stem cells, and by an absence of androgen receptor (AR) protein. Inhibition of BCRP-mediated efflux of dihydrotestosterone by novobiocin or fumitremorgin C in a rat prostate progenitor cell line that expresses BCRP and AR mRNAs, but minimal AR protein, results in stabilization and nuclear translocation of AR protein, providing a mechanism for lack of AR protein in BCRP-expressing stem cells. In both benign and malignant human prostate tissue, the rare epithelial cells that express BCRP and lack AR protein are localized in the basal cell compartment, survive androgen deprivation, and maintain proliferative potential in the hypoxic, androgen-deprived prostate. Putative prostate tumor stem cells that express BCRP but not AR protein in TRAMP are the source of a BCRP-negative and AR-negative, Foxa2- and SV40Tag-expressing, transit amplifying compartment that progresses to the poorly differentiated carcinomas that arise rapidly after castration. Therefore, BCRP expression isolates prostate stem/tumor stem cells from the prostate tissue microenvironment through constitutive efflux of androgen, protecting the putative tumor stem cells from androgen deprivation, hypoxia, or adjuvant chemotherapy, and providing the nidus for recurrent prostate cancer.
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PMID:Breast cancer resistance protein-mediated efflux of androgen in putative benign and malignant prostate stem cells. 1606 44

Radiation therapy is a main form of therapy for patients with localized prostate cancer. Despite advances in delivering radiation beams to the gland, urologists will be faced with managing patients with rising prostate-specific antigen values and radiation-recurrent cancer. If the cancer is detected early, salvage therapy can be initiated. Recent modifications in the technique of salvage cryosurgery have led to the ability to eradicate these tumors with a decrease in morbidity. The management and selection of these patients, as well as the results of salvage cryoablation, are discussed in this article.
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PMID:Selection of salvage cryotherapy patients. 1698 7

A significant number of men with prostate cancer will experience biochemical failure following treatment with primary radiation therapy. For patients with biopsy-proven recurrent cancer confined to the prostate, local salvage therapy may be a potentially curative treatment option. Most men, however, do not undergo local salvage therapy owing to difficulties in diagnosis as well as concerns over treatment-related complications in the salvage setting. Recently, improvements in technique and technology have substantially reduced the morbidity associated with locally ablative therapies, resulting in an increased interest in the use of minimally invasive therapies such as brachytherapy, cryotherapy, and high-intensity focused ultrasound in the salvage setting. Although these treatments are well tolerated, concerns remain over incomplete and inadequate treatment with locally ablative therapies. Future studies are required to appropriately select candidates for salvage ablative therapies and to determine the long-term oncologic efficacy of these treatments.
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PMID:Locally ablative therapies for primary radiation failures: a review and critical assessment of the efficacy. 1745 71

The application of Cre/loxP technology has resulted in a new generation of conditional mouse models of prostate cancer. Here, we describe the improvement of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or enhanced green fluorescent protein reporter line. In these models, the recombination mechanism that inactivates the Pten alleles also activates the reporter gene. In the luciferase reporter model, the growth of the primary cancer can be followed noninvasively by bioluminescence imaging (BLI). Surgical castration of tumor-bearing animals leads to a reduced bioluminescence signal corresponding to tumor regression that is verified at necropsy. When castrated animals are maintained, the emergence of androgen depletion-independent cancer is detected using BLI at times varying from 7 to 28 weeks postcastration. The ability to monitor growth, regression, or relapse of the tumor with the use of BLI lead to the collection of tumors at different stages of development. By comparing the distribution of phenotypically distinct populations of epithelial cells in cancer tissues, we noted that the degree of hyperplasia of cells with neuroendocrine differentiation significantly increases in the recurrent cancer relative to the primary cancer, a characteristic which may parallel the appearance of a neuroendocrine phenotype in human androgen depletion-independent cancer. The enhanced green fluorescent protein model, at necropsy, can provide an opportunity to locate or assess tumor volume or to isolate enriched populations of cancer cells from tumor tissues via fluorescence-based technologies. These refined models should be useful in the elucidation of mechanisms of prostate cancer progression, and for the development of approaches to preclinical intervention.
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PMID:Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence. 1767 Dec 24

High-intensity focused ultrasound (HIFU) is a minimally invasive alternative for patients with localized prostate cancer, not suitable for radical prostatectomy because of a life expectancy less than 10 years or because of major co-morbidities precluding surgery. HIFU can be performed in patients with LUTS (associated TURP) or with a previous history of BPH surgery. HIFU is repeatable after the initial procedure if a recurrent cancer is diagnosed on control biopsies. Furthermore, this therapy is a viable option for patients with a local relapse after external beam radiation therapy: oncologic efficacy is conversely related to the initial prostate cancer stage before radiation therapy.
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PMID:[Indications, techniques and outcomes of high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer]. 1826 50

The growing interest in high-intensity focused ultrasound (HIFU) technology is mainly due to its many potential applications as a new energy source and as noninvasive therapy. It has been introduced to urological oncology as a transrectal treatment for prostate cancer and as extracorporeal treatment for kidney cancer. Although its application in the kidney is still at the clinical feasibility phase, HIFU technology is currently being used in daily practice in Europe for the treatment of prostate cancer. Reports in the literature describing results of HIFU for prostate cancer are mainly based on monocentric, prospective clinical studies. The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and moderately differentiated tumors, as well as for local recurrence after external beam radiation. Two different devices for transrectal treatment of prostate cancer are available, which are essentially different in technology, application mode, published results, and side effects.HIFU in locally recurrent cancer after surgery, as well as adjuvant HIFU for local debulking in locally advanced or metastatic disease, shows promising first results for reducing local disease-induced morbidity and for delay of progression.
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PMID:[HIFU in urological oncology]. 1835 19

Magnetic resonance imaging (MRI) is the imaging tool of choice in the evaluation of prostate cancer. The main applications of MR imaging in the management of prostate cancer are: (1) to guide targeted biopsy when prostate cancer is clinically suspected and previous ultrasound-guided biopsy results are negative; (2) to localize and stage prostate cancer and provide a roadmap for treatment planning; and (3) to detect residual or locally recurrent cancer after treatment. Other MR techniques such as proton MR spectroscopic imaging (MRSI), diffusion-weighted imaging (DWI), and contrast-enhanced MRI (CE-MRI) complement conventional MR imaging by providing metabolic and functional information that can improve the accuracy of prostate cancer detection and characterization. In everyday clinical practice, and to account for patient comfort, MR imaging studies are limited to 1 h. To obtain consistently high-quality images, a well-designed protocol is necessary. Routine MR imaging can be supplemented by other MR techniques such as MRSI, DWI or CE-MRI depending on the expertise available and the clinical questions that need to be answered. This review summarizes the role of MR imaging in the management of prostate cancer and describes practical approaches to implementing anatomic, metabolic and functional MR imaging techniques in the clinic.
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PMID:MR imaging of the prostate in clinical practice. 1879 54

Interest in focal therapy for prostate cancer has recently been renewed owing to downward stage migration, improved biopsy and imaging techniques, and the prevalence of either unifocal cancer or a dominant cancer with secondary tumors of minimal malignant potential. Several techniques have potential for focal ablation of prostate cancer. Cryotherapy has been used for some time as primary therapy for complete ablation of the prostate or local recurrence after radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered by the uncertainty about complete ablation of the cancer, the frequent persistence of measurable prostate-specific antigen levels after the procedure, and a high rate of erectile dysfunction. Studies have reported "focal ablation" of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a cancer confined to that side with less risk of urinary or sexual complications. Whether cryotherapy has sufficient power to eradicate focal cancer and can be targeted with sufficient accuracy to avoid damage to surrounding structures remains to be demonstrated in prospective clinical trials. High-intensity focused ultrasound (HIFU) has been used widely in Europe for complete ablation of the prostate, especially in elderly men who are unwilling or unable to undergo radical therapy. For low- or intermediate-risk cancer, the short- and intermediate-term oncologic results have been acceptable but need confirmation in prospective multicenter trials presently underway. Whole gland therapy with transrectal ultrasound guidance has been associated with a high risk of acute urinary symptoms, often requiring transurethral resection before or after HIFU. Adverse effects on erectile function seem likely after a therapy that depends on heat to eradicate the cancer, but erectile function after HIFU has not been adequately documented with patient-reported questionnaires. HIFU holds promise for focal ablation of prostate cancer. As with cryotherapy, focal HIFU should reduce the adverse sexual, urinary, and bowel effects of whole gland ablation. New techniques are being developed to allow HIFU treatment under real-time guidance using magnetic resonance imaging, which could improve the precision and reduce the adverse effects further. Another promising technique, currently in clinical trials, is vascular-targeted photodynamic therapy, which has been used for whole gland ablation of locally recurrent cancer after radiotherapy and, more recently, for focal ablation of previously untreated cancer. In combination with a new, systemically administered photodynamic agent, laser light is delivered through fibers introduced into the prostate under ultrasound guidance. This technique does not heat the prostate but destroys the endothelial cells and cancer by activating the photodynamic agent. Damage to surrounding structures appears to be limited and can be controlled by the duration and intensity of the light. We have reviewed the principles of focal therapy and these new therapeutic modalities.
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PMID:New treatments for localized prostate cancer. 1909 27

Prostate cancer (PCa), with its potentially long latency, generally late-age onset, and high prevalence, is an ideal target for risk reduction and disease prevention strategies. Treatment of the disease is currently associated with significant side effects and reduced quality of life. Encouraging results are emerging in PCa risk reduction with 5alpha-reductase inhibitors (5-ARIs). The pivotal Prostate Cancer Prevention Trial (PCPT) with finasteride established the efficacy of 5-ARIs in reducing the period prevalence of PCa. Ongoing trials that will further clarify the role of 5-ARIs in preventing and treating PCa include the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) with dutasteride in PCa risk reduction; the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial on the effect of dutasteride on disease progression in low-grade localized PCa; and the Therapeutic Assessment of Rising PSAs [prostate-specific antigens] (TARP) trial on dutasteride in asymptomatic recurrent cancer. The data from these trials might initiate a paradigm shift in the attitudes of clinicians, healthcare policymakers, and patients to the benefits of PCa risk reduction strategies and their potential effect on a patient's health and quality of life.
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PMID:Overview of pivotal studies for prostate cancer risk reduction, past and present. 1937 25

Dynamic contrast-enhanced MRI enables noninvasive analysis of prostate vascularization as well as tumour angiogenesis and capillary permeability characteristics in prostate cancers. Pharmacokinetic models summarizing the complex information provided by signal intensity-time curves for a few quantitative pharmacokinetic parameters are increasingly being used in the routine clinical setting. This review consists of two parts. The first part discusses the advantages and disadvantages of the MR pulse sequences that can be used for performing DCE-MRI and also of the most widely used pharmacokinetic parameters and models and the parameters they describe. The second part outlines the range of current and potential future clinical applications of DCE-MRI and pharmacokinetic parametric maps in patients with prostate cancer, with reference to the current scientific literature on the topic. The potential clinical applications of DCE-MRI for prostate cancer include detection, localization, and staging, differentiation of recurrent cancer and estimation of the patient's prognosis, as well as monitoring of treatment response.
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PMID:Dynamic contrast-enhanced magnetic resonance imaging and pharmacokinetic models in prostate cancer. 2118 82


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